PROJECT SUMMARY/ABSTRACT The mission of TibaRay, Inc. is to develop and clinically translate next-generation radiation therapy technologies for the treatment of cancer, the single leading cause of death worldwide and increasing epidemically. A major advance in radiation therapy (RT) that has increased its curative potential and decreased side effects is the ability to sculpt radiation doses exquisitely in 3D to conform to tumors and spare surrounding healthy organs. This is achieved by delivering radiation beams to the tumor from multiple directions, each of which has an optimized spatial intensity distribution. However, the fastest treatment times are still minutes long, limited by both beam intensities in electron linacs and the mechanical systems that are used to direct and shape the beams. Recently, ultra-fast (<1s) high dose rate (300X) FLASH-RT has proven in pre-clinical studies to have high therapeutic index. But there is no existing technology to enable this therapy in the clinical, photon-based setting. To address these major shortcomings of current state-of-the-art radiation delivery systems, TibaRay has proposed a radical new design for RT systems, Pluridirectional High-energy Agile Scanning Electronic Radiotherapy (PHASER). It is based on patented, novel technologies to produce intensity-modulated therapeutic energy x-ray beams from multiple directions using no mechanical systems to direct (i.e. no rotating gantry) or shape the treatment beams (i.e. no mulit-leaf collimator). This is achieved by using an array of novel electron linacs each of which uses a magnetic electron beam scanning scheme paired with an extended bremsstrahlung target and multi-channel collimator array system referred to as Scanning Pencil-array-collimated High Speed Intensity-modulated X-ray source (SPHINX). Each of the novel linacs used in PHASER are far more efficient and will generate more beam than conventional medical linacs. In the full PHASER design, it is estimated that the treatment time can be reduced to <1s, effectively freezing physiological motion. The novel accelerator technology uses much simpler manufacturing techniques and production costs for PHASER are projected to be about the same as current state-of-the-art systems and maintenance/downtime costs should be lower. Initial proof of principle for the subsystems needed for PHASER have been demonstrated and design simulations have been performed in Phase 1. In Phase II, TibaRay, in partnership with the Stanford University Department of Radiation Oncology will optimize, build and test at first a single complete beam line with full maximum power. Then we will build and test a two-beam PHASER prototype to demonstrate the full rapid RF switching capability. These tests will be used to de-risk the primary working components of the system and will enable swift progress towards commercialization and clinical translation. Our novel technology will help fill a tremendous worldwide need for high-quality, cost-effective radiation therapy for cancer.